Mechanism and Regioselectivity of Intramolecular [2+2] Cycloaddition of Ene-Ketenes: A DFT Study

Intramolecular [2+2] cycloaddition of ene-ketenes gives either fused-ring (via normal [2+2] cycloaddition) or bridged-ring (via cross-[2+2] cycloaddition) cyclobutanones. For example, terminal ene-ketenes give the fused-ring cycloadducts, whereas dimethyl-substituted ene-ketenes furnish bridged-ring cycloadducts. For monomethyl-substituted ene-ketenes, both [2+2] cycloadducts are generated. However, there are no systematic theoretical studies on such regiochemistry in the literature. Herein, we report our DFT study on the mechanism and regioselectivity of these intramolecular [2+2] cycloadditions. DFT calculations reveal that both normal and cross-[2+2] cycloadditions are concerted processes. The normal [2+2] cycloaddition transition state is forming an internal carbocation while the cross-[2+2] cycloaddition transition state is generating an external carbocation (see Scheme 1 of the paper). On the basis of the relative stability of these carbocations, which is affected by both the tether and the substituent(s) on the alkene, a regiochemistry prediction model is proposed to understand and predict the reaction outcome.